Buffalo, NY—Patients with Type 1 diabetes improved blood sugar control and lost weight using a combination of three medications—dapagliflozin, liraglutide and insulin—instead of dual therapy, according to new research.

Results of the study were published recently in the Journal of Clinical Endocrinology & Metabolism.

“A majority of patients who have Type 1 diabetes do not have their blood glucose levels sufficiently controlled and monitored, and then they are left vulnerable to more complications of the disease,” said the study's senior author, Paresh Dandona, MD, PhD, SUNY Distinguished Professor and Chief of endocrinology, diabetes and metabolism in the Department of Medicine at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo in Buffalo, NY. “Our research found a triple therapy (insulin, liraglutide and dapagliflozin) approach led to impressive improvements in blood glucose control as well as weight loss. This strategy advances our previous work showing improvements in blood glucose management with the use of liraglutide in combination with insulin.”

The small randomized, placebo-controlled clinical trial involved 30 patients with type 1 diabetes; participants were between the ages of 18 and 75 and were already taking liraglutide and insulin to manage their diabetes. Researchers randomly assigned 20 of the patients to also receive 10 milligrams of dapaglifozin daily for 12 weeks, while the other 10 got a placebo.

Using continuous glucose monitors (CGMs) to track blood glucose levels, the study team tracked participants’ hemoglobin A1c (HbA1c), as well as their weight. Results indicate that HbA1c declined by 0.66% among participants who received the triple therapy; there was no significant change in the placebo group.

At the same time, patients receiving the triple therapy lost 1.9 kg, on average, with 14 of the 17 losing at least some weight. Weight remained unchanged among the placebo group.

In the dapagliflozin group, plasma concentrations of glucagon increased by an average of 35%, hormone-sensitive lipase by 29%, free fatty acids by 74%, acetoacetate by 67%, and beta-hydroxybutyrate by 254%, according to the article. Urinary ketone levels also increased significantly in the intervention group, while none of the changes was observed in the placebo group.

During the study, two of the participants on triple therapy developed diabetic ketoacidosis within 2 days of the daily dapagliflozin dose increasing to 10 mg from 5 mg. Both were withdrawn from the study.

“Our data also show for the first time that all patients on dapagliflozin experience an increase in ketones,” Dandona pointed out. “This may predispose people to developing diabetic ketoacidosis, particularly among those who have a marked reduction in insulin from taking liraglutide together with dapagliflozin and who have consumed too few carbohydrates. On the basis of the data, the dose reduction of insulin should be minimized and the higher dose of dapagliflozin should not be used in such patients. Our study sheds light on potential strategies for preventing diabetic ketoacidosis, but more research is still needed in this area.”

“Addition of dapagliflozin to insulin and liraglutide in patients with T1D results in a significant improvement in glycemia and weight loss while increasing ketosis,” study authors conclude. “If it is decided to use this approach, then it must be used only by a knowledgeable patient along with an endocrinologist who is well versed with it.”

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